The present invention relates to stable rhenium complexes which may be useful in the treatment of certain tumours.
Cisplatin and some platinum-based related drugs are known to be useful in the treatment of a variety of neoplastic diseases.
However, the clinical success of these drugs is limited by significant side effects, due in part, to the inherent toxicity of the platinum element (particularly, its nephrotoxicity).
In this respect, other transition metals have been contemplated for their use in pharmaceutical applications and rhenium (Re) has been postulated to be one of the least toxic.
Accordingly, rhenium-based compounds such as dirhenium clusters described in A. V. Shtemenko et al., Dalton Trans. (2009) 5132-5136 and azine-based rhenium complexes such as the ones described in I. Picón-Ferrer et al., J. Inorg. Biochem. 103 (2009) 94-100 have already been targeted as potential anti-tumour candidates which may be suitable to enter clinical development.
Several types of ligands for the rhenium metal are known. More particularly, a number of bidentate ligands have been described to form stable complexes with a single rhenium atom and show a propensity to cytotoxicity against various tumour cell lines.
Amongst these bidentate ligands it can be cited diimine ligands such as the ones depicted in D. K. Orsa et al., Inorg. Chem. Comm. 11 (2008) 1054-1056, diphenylphosphine ligands such as the ones described in J. Zhang et al., J. Organomet. Chem. 650 (2002) 123-132 or for example 2-(dimethylamino)ethoxide complexes proposed by Wenwu Wang et al. in Polyhedron 21 (2002) 1991-1999.